US 2001/0041344 A1Published application

Nonredundant split/pool synthesis of combinatorial libraries

AssigneeNanoscale Combinatorial Synthesis, Inc., 625 Clyde Avenue, Mountain View, CA 94043

InventorsNikolai F. Sepetov, Olga L. Issakova, Stephen A. Baum, James A. Ostrem

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Abstract

The present invention includes methods for generating combinatorial libraries on solid phase supports in which increased productivity is achieved by pooling all common steps in synthesis without using a tracking or coding system to record the synthetic history of each compound. Methods for generating combinatorial libraries in which containers with random mixtures of solid phase particles are divided and combined together in non-random ways without the exchange of particles between containers are also provided. Various products are optionally produced in multi-stage syntheses according to the invention, such as oligomers and synthetic non-repetitive organic molecules. The methods additionally relate to the identification of each library component without adding extra synthetic, physical, optical, or electronic encoding steps during library synthesis. Combinatorial synthetic systems are also provided.

Claims54

Dependent claims

A method of identifying selected members of a synthesized library of materials, comprising:

(a) providing at least n*m*f solid phase synthesis units, wherein n is equal to a number of choices of different first components in a first stage of synthesis, m is equal to a number of choices of different second components in a second stage of the synthesis, and f is equal to a number of solid phase synthesis units to comprise identical materials upon completion of the synthesis;
(b) segregating the solid phase synthesis units into n separate first stage reaction vessels, wherein each separate first stage reaction vessel comprises at least m*f solid phase synthesis units;
(c) reacting the solid phase synthesis units in each of the separate first stage reaction vessels with a different first component in the first stage of the synthesis;
(d) segregating the solid phase synthesis units of (c) into m separate second stage reaction vessels by distributing at least one of the solid phase synthesis units from each of the separate first stage vessels into each separate second stage reaction vessel such that each of the separate second stage reaction vessels comprises at least n*f solid phase synthesis units;
(e) reacting the solid phase synthesis units in each of the separate second stage reaction vessels with a different second component in the second stage of the synthesis, thereby synthesizing the library of the materials;
(f) detecting one or more distinguishing physical properties of selected members of the library;
and,
(g) identifying the selected members based on the one or more detected distinguishing physical properties.

5 more elements

A combinatorial library synthesis system, comprising:

(a) a plurality of reaction vessels;
(b) a handling system configured to translocate solid phase synthesis units and reagents to and from the plurality of reaction vessels;
(c) a detection system to detect one or more distinguishing physical properties of selected members of the combinatorial library;
and,
(d) a computer operably connected to the handling and detection systems, the computer comprising system software which directs the handling or detection systems to:
(i) segregate the solid phase synthesis units into n separate first stage reaction vessels to provide m*f solid phase synthesis units in each of the n vessels, wherein n is equal to a number of choices of different first components in a first stage of a library synthesis, m is equal to a number of choices of different second components in a second stage of the library synthesis, and f is equal to a number of solid phase synthesis units which comprise identical materials on completion of the library synthesis;
(ii) deliver one or more of the different first components to each of the n separate first stage reaction vessels, thereby providing for reaction of the different first components with the solid phase synthesis units to provide first stage reacted solid phase members;
(iii) segregate the first stage reacted solid phase members from the n separate first stage reaction vessels into m separate second stage reaction vessels by distributing at least one of the first stage reacted solid phase members from each of the separate first stage reaction vessels into each second stage reaction vessels such that each second stage reaction vessel comprises at least n*f solid phase synthesis units;
(iv) deliver one or more different second components to the second stage reaction vessels, thereby providing for reaction of the different second components with the first stage reacted solid phase members to provide the combinatorial library;
and,
(v) detect one or more distinguishing physical properties of the selected members of the combinatorial library.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/776,233Filed 2 Feb 2001
Priority: 3 Feb 2000
Published: 15 Nov 2001
Term ends: Not estimatedThe source records don’t support an estimate.

Classification32 codes

B01J 19/0046
Chemical, physical or physico-chemical processes in general; Their relevant apparatus: sequential or parallel reactions, e.g. for the synthesis of…
B01J 2219/00306
Features relating to reactor vessels: reactor vessels in a multiple arrangement
B01J 2219/00459
Dispensing or evacuation of the solid phase support: beads
B01J 2219/00468
Beads: by manipulation of individual beads